86 articles - From Friday Dec 16 2022 to Friday Dec 23 2022
Guidelines and related publications, position statements, white papers, technical reviews, consensus statements, etc…
| Blood Cancer J |
Consensus opinion from an international group of experts on measurable residual disease in hairy cell leukemia. Several assays including immunohistochemical analysis of bone marrow specimens, multi-parameter flow cytometry and molecular assays to detect the mutant BRAF V600E gene or the consensus primer for the immunoglobulin heavy chain gene (IGH) rearrangement have been utilized with few comparative studies. Here we provide a consensus report on the available data, the potential merits of MRD assessment in the front-line and relapse settings and recommendations on future role of MRD assessment in HCL. |
meta-analyses and systematic reviews
| Blood Adv |
Immunogenicity of SARS-CoV-2 vaccines in patients with multiple myeloma: a systematic review and meta-analysis. Patients with MM had low rates of humoral and cellular immune responses to the mRNA COVID-19 vaccines. Further studies are needed to determine the optimal doses of vaccines and evaluate the use of monoclonal antibodies for pre-exposure prophylaxis in this population. |
RCT, clinical trials, retrospective studies, etc…
| Ann Oncol |
Clonal KEAP1 mutations with loss of heterozygosity share reduced immunotherapy efficacy and low immune cell infiltration in lung adenocarcinoma. KEAP1 C-LOH mutations are associated with an immune-excluded phenotype and worse clinical outcomes among advanced LUAD patients treated with ICIs. By contrast, survival outcomes of patients whose tumors harbored KEAP1 CD-SC mutations were similar to those with KEAP1 wild-type LUADs. |
Durvalumab with or without tremelimumab versus the EXTREME regimen as first-line treatment for recurrent or metastatic squamous cell carcinoma of the head and neck: KESTREL, a randomized, open-label, phase III study. In patients with PD-L1-high expression, OS was comparable between durvalumab and the EXTREME regimen. Durvalumab alone, and with tremelimumab, demonstrated durable responses and reduced TRAEs versus the EXTREME regimen in R/M HNSCC. |
Germline-focused analysis of tumour-detected variants in 49,264 cancer patients: ESMO Precision Medicine Working Group recommendations. Strategic germline-focused analysis can prioritise a subset of tumour-detected variants for which germline follow-up will produce the highest yield of most actionable true germline variants. We present updated recommendations around germline follow-up of tumour-only sequencing including (i) revision to 5% for the minimum per-gene GCR, (ii) inclusion of actionable intermediate penetrance genes ATM and CHEK2 (iii) definition of a set of seven 'most-actionable' cancer susceptibility genes (BRCA1, BRCA2, PALB2, MLH1, MSH2, MSH6, RET) in which germline follow-up is recommended regardless of tumour type. |
Pembrolizumab monotherapy versus chemotherapy in platinum-pretreated, recurrent or metastatic nasopharyngeal cancer (KEYNOTE-122): an open-label, randomized, phase III trial. Pembrolizumab did not significantly improve OS compared with chemotherapy in participants with platinum-pretreated recurrent and/or metastatic NPC but did have manageable safety and a lower incidence of treatment-related adverse events. Clinical trial registry ClinicalTrials.gov, NCT02611960. |
Pembrolizumab versus cetuximab concurrent with radiotherapy in patients with locally advanced squamous cell carcinoma of head and neck unfit for cisplatin (GORTEC 2015-01 PembroRad): a multicenter, randomized, phase II trial. Compared with the SOC cetuximab-RT, pembrolizumab concomitant with RT did not improve the tumor control and survival but appeared less toxic in unfit patients with LA-SCCHN. |
| Blood |
Adenine base editor-mediated correction of the common and severe IVS1-110 (G>A) ß-thalassemia mutation. In HSPC-derived erythroid populations, this strategy was able to restore ß-globin production and correct inefficient erythropoiesis typically observed in ß-thalassemia both in vitro and in vivo. In conclusion, this proof-of-concept study paves the way for the development of a safe and effective autologous gene therapy approach for ß-thalassemia. |
Biology and therapeutic targeting of molecular mechanisms in MPN. However, better understanding of MPN biology has led to the development of rationally designed therapies, with the goal of not only addressing disease complications, but also potentially modifying disease course. We review the most recent data elucidating mechanisms of disease pathogenesis, and highlight emerging therapies that target MPN on several biologic levels, including JAK2-mutant MPN stem cells, JAK and non-JAK signaling pathways, mutant calreticulin and the inflammatory bone marrow microenvironment. |
Erythroid/megakaryocytic differentiation confers BCL-XL dependency and venetoclax resistance in acute myeloid leukemia. Combining BCL-XL inhibitor with the JAK inhibitor ruxolitinib showed synergistic and durable responses in cell lines. Our results suggest targeting BCL-XL as a potential therapy option in erythroid/megakaryoblastic leukemias and highlight an AML subgroup with potentially reduced sensitivity to venetoclax-based treatments. |
Overlapping features of therapy-related and de novoNPM1-mutated AML. Relapse-free survival did not differ between t-NPM1 and dn-NPM1 AML (HR 1.02, 95%CI 0.72-1.467, p=0.90) but was significantly higher in t-NPM1 AML than t-AML (HR 1.77, 95%CI 1.19-2.64, p=0.0045). t-NPM1 and dn-NPM1 AML have similar clinical, genomic and transcriptomic features, suggesting that they should be classified as a single disease entity. |
| Blood Adv |
Adaptation of Serious Illness Care Program to be Delivered via Telehealth for Older Patients with Hematologic Malignancy. The adapted SICP may provide older patients with AML and MDS an opportunity to share what matters most to them with their care team and may assist oncologists in aligning patient care with patient values. The adapted SICP is the subject of an ongoing single-arm pilot study at the Wilmot Cancer Institute. |
Characteristics of circulating KSHV-infected viroblasts during active KSHV+ multicentric Castleman disease. We also identified several putative mechanisms of immune escape used by KSHV, as KIV displayed an overall decrease of co-stimulatory molecules with a remarkable lack of CD40 expression and are IL-10 producing cells. The identification of this specific and easily accessible KSHV+ circulating population brings new elements in the understanding of KSHV-MCD but also raises new questions that need to be clarified. |
Chimeric antigen receptor T-cell therapy yields similar outcomes in patients with and without cytokine release syndrome. There was no significant difference in complete response or overall response rate between patients who did and did not develop CRS. In this retrospective analysis, we report that patients who develop CRS have similar clinical outcomes compared to patients without CRS treated with commercial anti-CD19 CAR T cells. |
Diminished Humoral and Cellular Responses to SARS-CoV-2 Vaccines in Patients with Chronic Lymphocytic Leukemia. In the booster vaccination cohort, positive correlations were seen between serologic response and CD4 T-cell responses for both variants (P = 0.58 Wuhan, P = 0.57 Omicron) and to a lesser degree for CD8 T-cell responses (P = 0.33 Wuhan, P = 0.22 Omicron). While no deaths from COVID-19 were reported after booster vaccinations, patients should use caution as newer variants emerge and escape vaccine-induced immunity. |
Dual targeting of aberrant DNA and histone methylation synergistically suppresses tumor cell growth in ATL. DUSP5 was downregulated by DNA methylation and H3K27me3 accumulation in the promoter region in HTLV-1-infected cells from ATL patients during ATL leukemogenesis. The present results demonstrate that dual targeting of aberrant DNA and histone methylation synergistically suppresses tumor cell growth by restoring DUSP5, and the dual targeting of aberrant DNA and histone methylation is a feasible therapeutic approach for ATL. |
Endoplasmic reticulum protein 5 attenuates platelet endoplasmic reticulum stress and secretion in a mouse model. The results also indicate a previously unanticipated role of platelet ER stress in platelet secretion and thrombosis. This may have important implications for therapeutic applications of ER stress inhibitors in thrombosis. |
Engineering amino acid uptake or catabolism promotes CAR-T cell adaption to the tumour environment. In turn we engineer and phenotype a further generation of CAR-T cells which express functional Arginase I/Arginase II enzymes, and have enhanced CAR-T cell proliferation and anti-tumour activity. Thus CAR-T cells can be adapted to the amino acid metabolic microenvironment of cancer, a hitherto recognised but unaddressed barrier to successful CAR-T therapy. |
Enriching single-arm clinical trials with external controls: possibilities and pitfalls. The validity of the treatment effect derived from indirect comparisons heavily depends on careful methodological considerations included in the proposed 3-step procedure. Because the level of evidence of a well-conducted RCT cannot be guaranteed, the evaluation is more important than in standard settings. |
External validation of the PEGED diagnostic algorithm for suspected pulmonary embolism in an independent cohort. Compared to standard algorithms, the PEGeD decreased the number of CTPA examinations. However, caution is required in patients with a low C-PTP and a D-dimer< 1000ng/mL but above their age-adjusted D-dimer cutoff. |
IL3-zetakine combined with a CD33 costimulatory receptor as a Dual CAR approach for safer and selective targeting of AML. Cytokine-Induced Killer (CIK) cells, co-expressing a first-generation low affinity anti-CD123 IL3-zetakine and an anti-CD33 as costimulatory receptor (CCR) without activation signaling domains, demonstrated a powerful antitumor efficacy against AML targets without any relevant toxicity on HSPCs and endothelial cells. The proposed optimized Dual CAR CIK strategy could offer the opportunity to unleash the potential of specifically target CD123+/CD33+ leukemic cells while minimizing toxicity against healthy cells. |
Impact of diagnosis to treatment interval in patients with newly diagnosed mantle cell lymphoma. We show that the DTI is an important prognostic factor in patients with newly diagnosed MCL and is strongly associated with adverse clinical factors and poor outcomes. DTI should be reported in al the newly diagnosed MCL patients who are enrolling in clinical trials and steps must be taken to ensure selection bias is avoided. |
Missense VKOR mutants exhibit severe warfarin resistance but lack VKCFD via shifting to an aberrantly reduced state. Increased activity also compensates for the weakened substrate binding caused by these mutations, thereby maintaining normal VKOR function. The uninhibitable nature of severe resistance mutations suggests that patients showing such signs should be genotyped and treated by alternative anticoagulation strategies. |
Nelarabine Combination Therapy for Relapsed or Refractory T-cell Acute Lymphoblastic Lymphoma/Leukemia. In a multivariable analysis, nelarabine combination therapy and alloSCT post nelarabine were associated with improved OS (HR 0.41, p 0.04 and HR 0.25, p 0.008). In conclusion, compared to monotherapy, nelarabine combination therapy was well tolerated and associated with improved survival in pediatric and adult patients with R/R T-ALL/LBL. |
Novel risk assessment for the intensity of conditioning regimen in elderly patients. In contrast, we found no significant differences in NRM between MAC and RIC in patients with a low RICE score (training cohort: HR, 0.99, 95%CI, 0.85-1.15, P = 0.860; validation cohort: HR, 0.81, 95%CI, 0.66-1.01, P = 0.061). In summary, a new and simple scoring system, the RICE score, appears to be useful for personalizing the conditioning intensity and might improve transplant outcomes in elderly patients. |
Obstetric and peri-operative management of patients with Factor XI deficiency: a retrospective observational study. There were no cases of epidural or spinal hematomas associated with neuraxial anesthesia. FXI levels remain stable during pregnancy and repeat measurements may not be necessary. |
Outcomes following posttransplant viral-specific T-cell therapy in patients with sickle cell disease. No immediate infusion-related toxicities occurred, and severe de novo acute GVHD occurred in only 2 (15.4%) patients. Given the good safety profile, high-rate of clinical responses and sustained remissions when administered with standard anti-viral treatments, the routine use of VSTs post-HSCT as prophylaxis or treatment may improve the overall safety of transplant for patients with SCD. |
Polatuzumab vedotin with infusional chemotherapy (Pola-DA-EPCH-R) for untreated aggressive B-cell non-Hodgkin lymphomas. Using Pola to replace vincristine in the DA-EPOCH-R regimen met its primary safety endpoint. These data support the further evaluation and use of this approach in histologies where the potential benefit of both an intensified regimen and Pola may be desired. |
Safety and efficacy of letetresgene autoleucel alone or with pembrolizumab for relapsed/refractory multiple myeloma. Two responders, but none of the non-responders, exhibited elevated cytokine levels post lete-cel infusion. Lete-cel had a manageable safety profile consistent with other lete-cel studies and demonstrated clear but transient antitumor activity in patients with RRMM. |
Venetoclax treatment in cancer patients has limited impact on circulating T and NK cells. By contrast, there was less impact on circulating T cells and natural killer (NK) cells, with no changes in their subset composition, transcriptome or function following venetoclax treatment. Our data indicate that venetoclax has minimal impact on circulating T or NK cells, supporting the rationale of combining this BH3 mimetic drug with cancer immunotherapies for more durable anti-tumour responses. |
| Blood Cancer J |
In-depth analysis of alternative splicing landscape in multiple myeloma and potential role of dysregulated splicing factors. We have developed a web portal that allows custom alternative splicing event queries by using gene symbols and visualizes AS events in MM and subgroups. Our portals can be accessed at and . |
Prognostic impact of the AML ELN2022 risk classification in patients undergoing allogeneic stem cell transplantation. In our study, the newly added group of patients with myelodysplasia-related gene mutations did not have adverse outcomes. Re-classifying these patients into the intermediate risk group and adjusting the grouping for al AML patients by MRD at HSCT, led to a refined and improved risk stratification, which should be validated in independent studies. |
Venetoclax with decitabine versus decitabine monotherapy in elderly acute myeloid leukemia: a propensity score-matched analysis. Of those who received DEC |
| Haematologica |
A phase 2, prospective, randomized, open-label study of defibrotide added to standard-of-care prophylaxis for the prevention of acute graft-versus-host disease after allogeneic hematopoietic cell transplantation. Overall survival rates at Day 180 post-transplant were similar between arms, as were the rates of serious treatment-emergent adverse events (defibrotide: 42%, SOC: 44%). While the observed differences in endpoints between the two arms were not substantial, these results suggest defibrotide prophylaxis may add a benefit to currently available SOC to prevent aGvHD following allo-HCT without adding significant toxicities. |
CCRL2 affects the sensitivity of myelodysplastic syndrome and secondary acute myeloid leukemia cells to azacitidine. In conclusion, we demonstrate that CCRL2 modulates epigenetic regulatory pathways, particularly DNMT levels, and affects MDS/sAML azacitidine sensitivity. These results support CCRL2 targeting as having MDS/sAML therapeutic potential. |
Exome sequencing in 116 patients with inherited thrombocytopenia that remained of unknown origin after systematic phenotype-driven diagnostic workup. Finally, ES-based Copy Number Variant (CNV) analysis disclosed an unexpected high prevalence of RUNX1 deletions, predisposing to hematological malignancies. Our findings demonstrate that ES, including CNV analysis, can substantially contribute to the diagnosis of IT and can solve diagnostic problems that would otherwise remain a challenge. |
Overexpression of the key metabolic protein CPT1A defines mantle cell lymphoma patients with poor response to standard high dose chemotherapy independent of MIPI and complement established high-risk factors. In addition to deregulated proliferation, we show that thermogenesis, fatty acid degradation and oxidative phosphorylation are altered in patients with poor survival, and that high expression of carnitine palmitoyltransferase 1A (CPT1A), an enzyme involved in fatty acid degradation, can specifically identify high-risk patients independent of the established high-risk factors. We suggest that complementary investigations of metabolism may increase the accuracy of patient stratification and that immunohistochemistry-based assessment of CPT1A can contribute to defining high-risk MCL. |
| Lancet Haematol |
Upfront autologous haematopoietic stem-cell transplantation versus carfilzomib-cyclophosphamide-dexamethasone consolidation with carfilzomib maintenance in patients with newly diagnosed multiple myeloma in England and Wales (CARDAMON): a randomised, phase 2, non-inferiority trial. Interpretation KCd did not meet the criteria for non-inferiority compared with autologous HSCT, but the marginal difference in progression-free survival suggests that further studies are warranted to explore deferred autologous HSCT in some subgroups, such as individuals who are MRD negative after induction. Funding Cancer Research UK and Amgen. |
| Leukemia |
A key role of the WEE1-CDK1 axis in mediating TKI-therapy resistance in FLT3-ITD positive acute myeloid leukemia patients. Remarkably, pharmacological inhibition of the WEE1 kinase synergizes and strengthens the pro-apoptotic effect of TKIs therapy in cell lines and patient-derived primary blasts. Finally, we propose a new molecular mechanism of TKIs resistance in AML and suggest the combination of WEE1 inhibitor and TKI as a therapeutic option to improve patients clinical outcome. |
A pro B cell population forms the apex of the leukemic hierarchy in Hoxa9/Meis1-dependent AML. Lentiviral overexpression of Sox4 and Bach2 induced dedifferentiation of H9M cells towards a lineage-negative state in vitro as the first step of lineage conversion. This work suggests that the potency to initiate a partial B lymphoid primed transcriptional program as present in infant AML correlates with aggressive disease and governs the H9M LSC hierarchy. |
Asxl1 deletion disrupts MYC and RNA polymerase II function in granulocyte progenitors. However, Asxl1 deletion results in a decrease in RNAPII promoter-proximal pausing in granulocyte progenitors, indicative of a global increase in productive transcription. These results suggest that ASXL1 inhibits productive transcription in granulocyte progenitors, identifying a new role for this epigenetic regulator in myeloid development. |
Dual inhibition of CHK1/FLT3 enhances cytotoxicity and overcomes adaptive and acquired resistance in FLT3-ITD acute myeloid leukemia. Moreover, 30 showed favorable druggability without significant blood toxicity or myelosuppression and exhibited a good oral PK profile with a T over 12 |
High-grade B-cell lymphoma (HGBL)-NOS is clinicopathologically and genetically more similar to DLBCL/HGBL-DH than DLBCL. Cases of HGBL-NOS frequently carry MYC-R and have a DH-like-Sig+. R-EPOCH induction in HGBL-NOS appears associated with improved OS compared with standard R-CHOP. |
Infectious complications after intensive chemotherapy with CLAG-M versus 7+3 for AML and other high-grade myeloid neoplasms. These data indicate that infections continue to cause substantial morbidity in patients treated for AML, especially those treated for relapsed/refractory disease, and are more common with newer, more myelosuppressive regimens such as CLAG-M. Improved strategies for infection prevention are needed. |
Invasive fungal diseases impact on outcome of childhood ALL - an analysis of the international trial AIEOP-BFM ALL 2009. Our data define older children with ALL and those with insufficient treatment-response at high risk for IFD. As we show that IFD is an independent risk factor for event-free and overall survival, these patients may benefit from targeted antifungal prophylaxis. |
Tumorigenic role of Musashi-2 in aggressive mantle cell lymphoma. MSI2-knockdown cells had reduced tumorigenic engraftment into mice bone marrow and spleen compared to control cells in xenotransplanted mouse models. Our results suggest that MSI2 might play a key role in sustaining stemness and tumor cell survival, representing a possible novel target for therapeutic interventions in MCL. |
| Thromb Haemost |
Drug-Drug Interaction between Antiplatelet Therapy and Lipid-Lowering Agents (Statins and PCSK9 Inhibitors). PCSK9 antibodies target a serine protease (PCSK9), which promotes the degradation of the LDL-C receptor impacting on LDL-C plasma levels and (ox)LDL-C-receptor-mediated signaling in platelets similar to but more potent than statins. These functionally synergistic actions are the basis for numerous interactions between antiplatelet and these lipid-lowering drugs, which may, in summary, reduce the incidence of atherothrombotic vascular events. |
How Did We Get Here? Antithrombotic Therapy after Bioprosthetic Aortic Valve Replacement: A Review. and relevance Insufficient antithrombotic therapy after bioprosthetic aortic valve replacement has serious implications ischemic stroke, systemic arterial thromboembolism, and clinical and subclinical valve thromboses. Unnecessarily intense antithrombotic therapy, however, increases risk of bleeding and associated morbidity and mortality. Professional bodies have used the current low-quality evidence and generated incongruent recommendations. Researchers should prioritize generating high-quality, randomized evidence evaluating the risks and benefits of antiplatelet versus anticoagulant therapy after bioprosthetic aortic valve replacement. |
Plenty of the editorials are available as full text through the publisher website using the provided link
| Blood |
| Blood Cancer J |
Management of patients with lower-risk myelodysplastic syndromes. In this review, we focus on the diagnosis, prognosis, and treatment options, as well as the prediction of the disease course and monitoring of treatment response in patients with LR-MDS. We discuss how next-generation sequencing, increasing knowledge on mechanisms of MDS pathogenesis, and novel therapies may change the current treatment landscape in LR-MDS and why structured assessments of responses, toxicities, and patient-reported outcomes should be incorporated into routine clinical practice. |
| CA Cancer J Clin |
Cancer care for people with dementia: Literature overview and recommendations for practice and research. The authors propose that optimal cancer care for PLWD should focus on proactively minimizing these risk areas and thus must be highly person-centered, with holistic decision making, individualized reasonable adjustments to practice, and strong inclusion and support of family carers. Comprehensive recommendations are made for clinical practice and future research to help clinicians and providers deliver best and equitable cancer care for PLWD and their families. |
Cancer epigenetics in clinical practice. Moreover, the reversibility of epigenetic modifications, in contrast to the irreversibility of genetic changes, has made the epigenetic machinery an attractive target for drug development. This review summarizes the most advanced applications of epigenetic biomarkers and epigenetic drugs in the clinical setting, highlighting commercially available DNA methylation-based assays and epigenetic drugs already approved by the US Food and Drug Administration. |
| Haematologica |
Biosimilars in rare diseases - a focus on paroxysmal nocturnal hemoglobinuria. As prescription drug spending has increased and exclusivity periods have expired, manufacturers have developed biosimilars-biologics that may be more affordable and highly similar to a licensed biological therapeutic, with no clinically meaningful differences in safety or efficacy. With biosimilars gaining regulatory approval around the globe and broadening patient access to biologics, this review aims to help rare disease healthcare providers familiarize themselves with biosimilars, understand their development and regulatory approval process, and address practical considerations that may facilitate their use. |
| Leukemia |
misc publications eg case reports, tools of the trade, images of the month, etc…
| Am J Hematol |
| Blood |
| Blood Adv |
| Lancet Haematol |
| Leukemia |
Letters to the editors and authors’ replies
| Am J Hematol |
| Ann Oncol |
| Blood Cancer J |
| Haematologica |
| J Hematol Oncol |
A novel tRNA-derived fragment tRF-3022b modulates cell apoptosis and M2 macrophage polarization via binding to cytokines in colorectal cancer. Mechanistically, we found that tRF-3022b binds to galectin 1 (LGALS1) and macrophage migration inhibitory factor (MIF) in CRC cells and reduces polarization by regulating MIF in M2 macrophages. In conclusion, our study revealed the expression pattern of tRFs in both tissue and plasma exosomes and identified a novel tRF, tRF-3022b, which may affect CRC tumor growth and M2 macrophage polarization by binding to LGALS1 and MIF. |